Research

10 pages, 601 KiB

Open AccessArticle

A Retrospective Study on the Efficacy of Subcutaneous Immunoglobulin as Compared to Intravenous Formulation in Patients with Chronic Lymphocytic Leukemia and Secondary Antibody Deficiency

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Andrea Visentin

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Maria Chiara Molinari

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Stefano Pravato

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Alessandro Cellini

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Francesco Angotzi

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Chiara Adele Cavaretta

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Francesca Romana Mauro

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Livio Trentin

Curr. Oncol. 2023, 30(1), 274-283; https://doi.org/10.3390/curroncol30010022 - 25 Dec 2022

Cited by 4 | Viewed by 1837

Abstract

Secondary antibody deficiency (SAD) is a common complication in chronic lymphocytic leukemia (CLL) which favors the development of life-threatening infections. Subcutaneous immunoglobulins (IG) (SCIG) have been proven to be as effective as intravenous immunoglobulin (IVIG) in primary immunodeficiencies. Since only a few studies [...] Read more.

Secondary antibody deficiency (SAD) is a common complication in chronic lymphocytic leukemia (CLL) which favors the development of life-threatening infections. Subcutaneous immunoglobulins (IG) (SCIG) have been proven to be as effective as intravenous immunoglobulin (IVIG) in primary immunodeficiencies. Since only a few studies investigated SCIG in secondary antibody deficiency, the aim of this study was to assess the efficacy and safety of SCIG or IVIG in CLL patients with secondary antibody deficiency. One hundred and sixteen CLL patients were recruited, 63% were males, and the median age was 68 years; 44% had bronchiectasis and 76% never smoked. Forty-nine patients received IVIG and 88 SCIG, including 28 patients who shifted from IVIG to SCIG. Despite similar baseline IgG levels, patients receiving SCIG achieved higher IgG after at least +6 months (p = 0.0009). We observed that SCIG can decrease the cumulative incidence of first (HR 0.39 p < 0.0001) and second (HR 0.56 p = 0.0411) infection more than IVIG. The effect was remarkable in that patients were able to reach at least 6 g/L of IgG after 6 months of treatments (p < 0.0001). Replacement therapies were well tolerated with less adverse events and a lower discontinuation rate in patients was managed with SCIG than IVIG. In this study we describe the clinical features of a large cohort of CLL with secondary antibody deficiency receiving IG. We demonstrated that SCIG are active and well tolerated drugs that allows to reach higher IgG levels and decrease the rate of infections better than IVIG, in particular when IgG levels reach 6 g/L. Full article

(This article belongs to the Special Issue Chronic Lymphocytic Leukemia: Therapy and Outcome)

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15 pages, 984 KiB

Open AccessArticle

Effect of Lenalidomide Maintenance in Chronic Lymphocytic Leukemia: A Meta-Analysis and Trial-Sequential Analysis

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Curr. Oncol. 2022, 29(6), 4245-4259; https://doi.org/10.3390/curroncol29060339 - 14 Jun 2022

Viewed by 1682

Abstract

Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disease in adults. Despite durable responses and sustained remission rates to frontline therapy, CLL is still incurable within standard therapy and eventually relapses. Maintenance therapies aim to achieve deep remission. However, the efficacy and [...] Read more.

Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disease in adults. Despite durable responses and sustained remission rates to frontline therapy, CLL is still incurable within standard therapy and eventually relapses. Maintenance therapies aim to achieve deep remission. However, the efficacy and safety of lenalidomide maintenance are still debated. Randomized controlled trials published before March 2022 were retrieved from databases. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Trial sequential analysis examined analytical power in primary outcomes. Secondary outcomes were Grade 3–4 neutropenia, treatment discontinuation (TD), serious adverse events (SAE), and fatal adverse events (FAE). Hazard (HR) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Four articles (733 patients) met the selection criteria. Lenalidomide maintenance was associated with a statistically significant effect in prolonging PFS (HR, 0.43; 95% CI, 0.28–0.68; I² = 57%) and higher proportion of SAE (OR 4.64; 95% CI 2.96–7.26; I² = 0%) and exhibited no difference in OS (HR, 0.62; 95% CI, 0.29–1.30; I² = 52%) observation/placebo. It showed no significant difference compared with observation/placebo regarding Grade 3–4 neutropenia (OR 2.30; 95% CI 0.84–6.28; I² = 81%), TD (OR 0.76; 95% CI 0.29–1.99; I² = 84%), and FAE (OR 0.86; 95% CI 0.28–2.63; I² = 0%). Lenalidomide maintenance can prolong PFS in CLL. Further studies should verify its effect on OS. Full article

(This article belongs to the Special Issue Chronic Lymphocytic Leukemia: Therapy and Outcome)

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10 pages, 778 KiB

Open AccessArticle

Invasive Fungal Disease in Patients with Chronic Lymphocytic Leukemia in Japan: A Retrospective Database Study

by

Takeo Yasu

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Kotono Sakurai

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Manabu Akazawa

Curr. Oncol. 2022, 29(5), 3242-3251; https://doi.org/10.3390/curroncol29050264 - 04 May 2022

Cited by 1 | Viewed by 1670

Abstract

Invasive fungal disease (IFD) is an important cause of morbidity and mortality in patients with hematological malignancies. As chronic lymphocytic leukemia (CLL) is a rare hematological malignancy in Japan, IFD incidence in Japanese patients with CLL is unclear. This study aimed to investigate [...] Read more.

Invasive fungal disease (IFD) is an important cause of morbidity and mortality in patients with hematological malignancies. As chronic lymphocytic leukemia (CLL) is a rare hematological malignancy in Japan, IFD incidence in Japanese patients with CLL is unclear. This study aimed to investigate IFD incidence in Japanese patients with CLL. This retrospective cohort study used data of patients with CLL registered between April 2008 and December 2019 in the Medical Data Vision database (n = 3484). IFD incidence after CLL diagnosis in the watch-and-wait (WW) and drug therapy (DT) groups was 1.5% and 9.2%, respectively. The most common type of IFD was invasive aspergillosis (28.1%). Cox proportional hazards multivariate analysis revealed that DT (hazard ratio [HR]: 2.13) and steroid use (HR: 4.19) were significantly associated with IFD occurrence. IFD incidence was significantly higher in the DT group than in the WW group (log-rank p < 0.001); however, there was no significant between-group difference in the time to IFD onset or the type of IFD (p = 0.09). This study determined the incidence of IFD in patients with CLL during WW. Physicians should monitor for IFD, even among patients with CLL undergoing the WW protocol. Full article

(This article belongs to the Special Issue Chronic Lymphocytic Leukemia: Therapy and Outcome)

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13 pages, 1561 KiB

Open AccessArticle

Overcoming of Microenvironment Protection on Primary Chronic Lymphocytic Leukemia Cells after Treatment with BTK and MDM2 Pharmacological Inhibitors

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Curr. Oncol. 2021, 28(4), 2439-2451; https://doi.org/10.3390/curroncol28040223 - 01 Jul 2021

Cited by 2 | Viewed by 2331

Abstract

In B-chronic lymphocytic leukemia (B-CLL), the interaction between leukemic cells and the microenvironment promotes tumor cell survival. The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib is one of the first-in-class molecules for the treatment of B-CLL patients; however, the emerging mechanisms of resistance to [...] Read more.

In B-chronic lymphocytic leukemia (B-CLL), the interaction between leukemic cells and the microenvironment promotes tumor cell survival. The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib is one of the first-in-class molecules for the treatment of B-CLL patients; however, the emerging mechanisms of resistance to ibrutinib call for new therapeutic strategies. The purpose of the current study was to investigate the ability of ibrutinib plus the MDM2-inhibitor nutlin-3 to counteract the tumor microenvironment protective effect. We observed that primary B-CLL cells cultivated in microenvironment mimicking conditions were protected from apoptosis by the up-regulation of c-MYC and of p53. In the same setting, combined treatments with ibrutinib plus nutlin-3 led to significantly higher levels of apoptosis compared to the single treatments, counteracting the c-MYC up-regulation. Moreover, the combination induced high p53 levels and a significant dissipation of the mitochondrial membrane potential, together with BAX cleavage in the more active p18 form and phospho-BAD down-regulation, that are key components of the mitochondrial apoptotic pathway, enhancing the apoptosis level. Our findings propose a new therapeutic strategy to overcome the tumor microenvironment protection involved in B-CLL resistance to drugs, with possible clinical implications also for other hematologic and solid tumors for which ibrutinib is considered a therapeutic option. Full article

(This article belongs to the Special Issue Chronic Lymphocytic Leukemia: Therapy and Outcome)

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Review

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11 pages, 1669 KiB

Open AccessReview

CAR T Cell Therapy for Chronic Lymphocytic Leukemia: Successes and Shortcomings

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Aleksandar Arsenijevic

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Jelena Milovanovic

Curr. Oncol. 2022, 29(5), 3647-3657; https://doi.org/10.3390/curroncol29050293 - 18 May 2022

Cited by 11 | Viewed by 3443

Abstract

Chimeric antigen receptor T (CAR T) cell therapy achieved remarkable success in B-cell leukemia and lymphoma which led to its incorporation in treatment protocols for these diseases. CAR T cell therapy for chronic lymphocytic leukemia (CLL) patients showed less success compared to other [...] Read more.

Chimeric antigen receptor T (CAR T) cell therapy achieved remarkable success in B-cell leukemia and lymphoma which led to its incorporation in treatment protocols for these diseases. CAR T cell therapy for chronic lymphocytic leukemia (CLL) patients showed less success compared to other malignant tumors. In this review, we discuss the published results regarding CAR T cell therapy of CLL, possible mechanisms of failures and expected developments. Full article

(This article belongs to the Special Issue Chronic Lymphocytic Leukemia: Therapy and Outcome)

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Other

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7 pages, 1533 KiB

Open AccessCase Report

Therapeutic Management of Chronic Lymphocytic Leukemia Presenting with Recurrent Massive Ascites

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Curr. Oncol. 2022, 29(10), 6787-6793; https://doi.org/10.3390/curroncol29100534 - 22 Sep 2022

Cited by 1 | Viewed by 1661

Abstract

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative malignancy that is categorized by the production and accumulation of CD5+ monoclonal B cell lymphocytes, commonly in the spleen, bone marrow, and peripheral blood; these are morphologically mature lymphocytes with abnormal immune function. Ascites, although common [...] Read more.

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative malignancy that is categorized by the production and accumulation of CD5+ monoclonal B cell lymphocytes, commonly in the spleen, bone marrow, and peripheral blood; these are morphologically mature lymphocytes with abnormal immune function. Ascites, although common in solid organ malignancies such as ovarian, breast, and gastrointestinal, is a rare clinical manifestation in hematological malignancies. The case presented herein describes an elderly male patient with CLL who presented with transudative ascites 7 years after the completion of chemotherapy. Microscopic analysis and flow cytometry of the patient’s ascitic fluid were consistent with CLL, and he was treated with six cycles of obinutuzumab immunotherapy with the addition of acalabrutinib, resulting in near resolution of malignant ascites. A few cases have reported CLL manifesting as transudative or exudative ascites in elderly patients. A few previous cases have reported the development of ascites between 12 and 21 months after the initial treatment of CLL with chemotherapy. A unique feature of our patient is the presentation with malignant ascites nearly 7 years after the initial CLL treatment with chemotherapy. The intent of this case report is to bring awareness of ascites as a possible initial presenting symptom of CLL in patients with isolated abdominal distention with or without common clinical features of leukemia (i.e., splenomegaly, lymphadenopathy, and B-symptoms) and the therapeutic management thereafter. Malignant ascites may be associated with relapse or the transformation of leukemia; thus, prompt diagnosis and treatment should not be delayed. Full article

(This article belongs to the Special Issue Chronic Lymphocytic Leukemia: Therapy and Outcome)

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6 pages, 696 KiB

Open AccessCase Report

Two Distinct Clinical Patterns of Ibrutinib-to-Venetoclax Transition in Relapsed Chronic Lymphocytic Leukemia Patients

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Curr. Oncol. 2022, 29(4), 2792-2797; https://doi.org/10.3390/curroncol29040227 - 15 Apr 2022

Cited by 1 | Viewed by 2062

Abstract

Patients with chronic lymphocytic leukemia (CLL) relapsing on ibrutinib are often treated with the Bcl-2 inhibitor venetoclax. However, the transition from one agent to another poses some clinical challenges due to disease flares sometimes occurring right after ibrutinib interruption. Here, we describe three [...] Read more.

Patients with chronic lymphocytic leukemia (CLL) relapsing on ibrutinib are often treated with the Bcl-2 inhibitor venetoclax. However, the transition from one agent to another poses some clinical challenges due to disease flares sometimes occurring right after ibrutinib interruption. Here, we describe three clinical vignettes highlighting two distinct patterns of ibrutinib-to-venetoclax transition. While patients following the favorable pattern transited to venetoclax without experiencing disease flare, the one patient who took the unfavorable path showed rapid disease rebound, with large-cell transformation occurring one week after ibrutinib interruption. A high burden of BTK and PLCG2 mutations was found only in patients with the favorable transition pattern, suggesting that removing BTK inhibition might be particularly harmful if CLL cells are progressing through mechanisms external to the BTK axis. Full article

(This article belongs to the Special Issue Chronic Lymphocytic Leukemia: Therapy and Outcome)

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6 pages, 2263 KiB

Open AccessCase Report

Primary Myelofibrosis Occurring during Targeted Therapy for Chronic Lymphocytic Leukemia: A Report of Two Cases

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Curr. Oncol. 2022, 29(3), 1455-1460; https://doi.org/10.3390/curroncol29030122 - 27 Feb 2022

Viewed by 2531

Abstract

The disease course of chronic lymphocytic leukemia (CLL) is frequently characterized by the occurrence of various complications, such as second primary cancer, which can impact patients’ prognoses. While therapies for CLL have evolved tremendously in the past decades, overlooking the possibility of rare [...] Read more.

The disease course of chronic lymphocytic leukemia (CLL) is frequently characterized by the occurrence of various complications, such as second primary cancer, which can impact patients’ prognoses. While therapies for CLL have evolved tremendously in the past decades, overlooking the possibility of rare neoplasms that arise along with CLL may hinder the benefit that these therapies grant to patients. Moreover, the ability of newer therapies to alter the landscape of these complications is still largely unknown. Primary myelofibrosis (PMF) is not commonly associated with CLL, with only a few cases reported in the literature, with little information regarding the clinico-biological features and the optimal management for these associated conditions. Here, we report two unusual cases of PMF that occurred a few months after the start of therapy for CLL with targeted agents (ibrutinib and venetoclax). Both cases represented a diagnostic and therapeutic challenge, underscoring the need for clinicians to remain vigilant about the possible co-occurrence of these two hematological malignancies, especially in the era of targeted therapy for CLL. Full article

(This article belongs to the Special Issue Chronic Lymphocytic Leukemia: Therapy and Outcome)

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